An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer
文献类型：期刊论文
| 作者 | Li, Hongwen5; Yu, Chao3; Jiang, Jing2; Huang, Changjiang3; Yao, Xuejing5; Xu, Qiaoyu3; Yu, Fang3; Lou, Liguang4 ; Fang, Jianmin1,5,6
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| 刊名 | CANCER BIOLOGY & THERAPY
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| 出版日期 | 2016 |
| 卷号 | 17期号:4页码:346-354 |
| 关键词 | Antibody drug conjugate gastric cancer HER2 monomethyl auristatin E target therapy |
| ISSN号 | 1538-4047 |
| DOI | 10.1080/15384047.2016.1139248 |
| 文献子类 | Article |
| 英文摘要 | Antibody-drug conjugate (ADC) is a novel class of therapeutics for cancer target therapy. This study assessed antitumor activity of ADC with an antimitotic agent, monomethyl auristatin E (MMAE) and a humanized monoclonal anti-HER2 antibody, hertuzumab, in gastric cancer. The efficacy of hertuzumab-MC-Val-Cit-PAB-MMAE (hertuzumab-vcMMAE) on human epidermal growth factor receptor 2 (HER2) positive human gastric cancer cells, NCI-N87, was evaluated in vitro and in vivo. The cytotoxicity of hertuzumab was significantly enhanced after conjugation with MMAE. Compared to trastuzumab, hertuzumab had a higher affinity to HER2 and had more potent antibody-dependent cell-mediated cytotoxicity (ADCC) activity in vitro. After conjugation with MMAE, the binding specificity for HER2 was not affected. Furthermore, the internalization of hertuzumab-vcMMAE in HER2 positive gastric cancer cells was verified. Although the conjugation of hertuzumab and MMAE decreased the ADCC effect, the overall cytotoxicity was dramatically increased in HER2 positive gastric cancer cells. In vitro data on this hertuzumab-vcMMAE has exerted much stronger antitumor activity compared to trastuzumab-DM1 in HER2 positive gastric cancer cells. A single administration of hertuzumab-vcMMAE at 5 or 10mg/kg showed high potency and a sustained tumor inhibitory effect on NCI-N87 xenografts in mice. In conclusion, hertuzumab-vcMMAE conjugate is a highly effective anti-HER2 targeted therapy for HER2-positive gastric cancer. |
| WOS关键词 | POTENT ANTITUMOR-ACTIVITY ; RESISTANT BREAST-CANCER ; DRUG CONJUGATE ; PROGNOSTIC-SIGNIFICANCE ; PROSTATE-CANCER ; HER2 STATUS ; PHASE-II ; TRASTUZUMAB ; THERAPY ; CELLS |
| 资助项目 | National Science and Technology Major Project of China[2014ZX09508004001] ; National Science and Technology Major Project of China[2013ZX09401002] ; National Basic Research of China 973 program[2015cb553706] ; National Natural Science Foundation of China[31270987] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000375583500003 |
| 出版者 | TAYLOR & FRANCIS INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276228]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Fang, Jianmin |
| 作者单位 | 1.Tongji Univ, Suzhou Inst, Suzhou, Jiangsu, Peoples R China; 2.Binzhou Med Univ, Sch Pharm, Yantai, Shandong, Peoples R China; 3.RemeGen Ltd, Yantai, Shandong, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China; 5.Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China; 6.Sichuan Univ, West China Hosp, Collaborat Innovat Ctr Biotherapy, Chengdu 610064, Sichuan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Hongwen,Yu, Chao,Jiang, Jing,et al. An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer[J]. CANCER BIOLOGY & THERAPY,2016,17(4):346-354. |
| APA | Li, Hongwen.,Yu, Chao.,Jiang, Jing.,Huang, Changjiang.,Yao, Xuejing.,...&Fang, Jianmin.(2016).An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer.CANCER BIOLOGY & THERAPY,17(4),346-354. |
| MLA | Li, Hongwen,et al."An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer".CANCER BIOLOGY & THERAPY 17.4(2016):346-354. |
入库方式： OAI收割
来源：上海药物研究所
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